Crystalline salt forms of n-((1-(2-(tert-butylamino)-2-oxoethyl)piperidin-4-yl) methyl)-3-chloro-5-fluorobenzamide and methods of use thereof

Abstract

Described herein, in part, are crystalline and salt forms of N-((1-(2-(tert-butylamino)-2-oxoethyl)piperidin-4-yl)methyl)-3-chloro-5-fluorobenzamide useful for preventing and/or treating a disease or condition relating to aberrant function of a T-type calcium channel, such as epilepsy and epilepsy syndromes (e.g., absence seizures, juvenile myoclonic epilepsy, or a genetic epilepsy), tremor (e.g., essential tremor), and psychiatric disorder (e.g., mood disorders (e.g., major depressive disorder)).

1 . A salt of Compound 1, wherein Compound 1 is represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
       and wherein the salt is selected from the group consisting of acetate salt, adipate salt, alginate salt, ascorbate salt, asparatate salt, besylate salt, benzoate salt, citrate salt, cyclamate salt, edisylate salt, esylate salt, isethionate salt, fumarate salt, gentisate salt, gluconate salt, glucuronate salt, glutamate salt, glutarate salt, ketoglutarate salt, glycolate salt, hippurate salt, lactobionate salt, maleate salt, malate salt, malonate salt, mesylate salt, napadisylate salt, napsylate salt, oleate salt, oroate salt, oxalate salt, pamoate salt, phosphate salt, sebacate salt, succinate salt and tartrate salt. 
     
     
         2 . A crystalline form of a salt of Compound 1, wherein Compound 1 is represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
       and wherein the salt is selected from the group consisting of adipate salt, besylate salt, cyclamate salt, edisylate salt, esylate salt, fumarate salt, glutarate salt, glycolate salt, inappendiculate salt, napsylate salt, orotate salt, oxalate salt, maleate salt, malonate salt, mesylate salt, pamoate salt, phosphate salt, and sebacate salt. 
     
     
         3 . The crystalline form of  claim 2 , wherein the salt is edisylate salt, and wherein the crystalline form is Form 1 characterized by an X-ray powder diffraction pattern (XRPD pattern) that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 1. 
     
     
         4 - 5 . (canceled) 
     
     
         6 . The crystalline form of  claim 2 , wherein the salt is esylate salt, and wherein the crystalline form is Form 2 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 2. 
     
     
         7 - 8 . (canceled) 
     
     
         9 . The crystalline form of  claim 2 , wherein the salt is glutarate salt, and wherein the crystalline form is Form 3 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 3. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . The crystalline form of  claim 2 , wherein the salt is napadisylate salt, and wherein the crystalline form is Form 4 characterized by an X-ray powder diffraction pattern (XRPD pattern) that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 4. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . The crystalline form of  claim 2 , wherein the salt is napsylate salt, and wherein the crystalline form is Form 5 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 5. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The crystalline form of  claim 2 , wherein the salt is orotate salt, and wherein the crystalline form is Form 6 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 6. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . The crystalline form of  claim 2 , wherein the salt is maleate salt, and wherein the crystalline form is Form 7 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 7. 
     
     
         22 - 24 . (canceled) 
     
     
         25 . The crystalline form of  claim 2 , wherein the salt is malonate salt, and wherein the crystalline form is Form 8 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 8. 
     
     
         26 - 28 . (canceled) 
     
     
         29 . The crystalline form of  claim 2 , wherein the salt is mesylate salt, and wherein the crystalline form is Form 9 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 9. 
     
     
         30 - 32 . (canceled) 
     
     
         33 . The crystalline form of  claim 2 , wherein the salt is pamoate salt, and wherein the crystalline form is Form 10 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 10. 
     
     
         34 - 36 . (canceled) 
     
     
         37 . The crystalline form of  claim 2 , wherein the salt is adipate salt, and wherein the crystalline form is Form 11 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 11. 
     
     
         38 - 39 . (canceled) 
     
     
         40 . The crystalline form of  claim 2 , wherein the salt is besylate salt, and wherein the crystalline form is Form 12 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 12. 
     
     
         41 - 42 . (canceled) 
     
     
         43 . The crystalline form of  claim 2 , wherein the salt is cyclamate salt, and wherein the crystalline form is Form 13 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 13. 
     
     
         44 - 45 . (canceled) 
     
     
         46 . The crystalline form of  claim 2 , wherein the salt is fumarate salt, and wherein the crystalline form is Form 14 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 14. 
     
     
         47 - 48 . (canceled) 
     
     
         49 . The crystalline form of  claim 2 , wherein the salt is glycolate salt, and wherein the crystalline form is Form 15 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 15. 
     
     
         50 - 51 . (canceled) 
     
     
         52 . The crystalline form of  claim 2 , wherein the salt is oxalate salt, and wherein the crystalline form is Form 16 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 16. 
     
     
         53 - 54 . (canceled) 
     
     
         55 . The crystalline form of  claim 2 , wherein the salt is phosphate salt, and wherein the crystalline form is Form 17 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 17. 
     
     
         56 - 57 . (canceled) 
     
     
         58 . The crystalline form of  claim 2 , wherein the salt is sebacate salt, and wherein the crystalline form is Form 18 characterized by an XRPD pattern that includes at least one peak at the diffraction angle (° 2θ) selected from the group of peaks listed in Table 18. 
     
     
         59 - 60 . (canceled) 
     
     
         61 . A pharmaceutical composition comprising the salt of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         62 - 65 . (canceled) 
     
     
         66 . A method of treating a neurological disorder comprising administering to a subject in need thereof the salt of  claim 1 . 
     
     
         67 - 69 . (canceled) 
     
     
         70 . A method of treating a movement disorder in a subject in need thereof, said method comprising administering to said subject the salt of  claim 1 . 
     
     
         71 . The method of  claim 66 , wherein the neurological disorder is tremor. 
     
     
         72 . The method of  claim 71 , wherein the tremor is essential tremor.